Process for the preparation of saligenol

ABSTRACT

Saligenol is obtained by electrochemical reduction of salicylic acid in a cell in which the anolyte and catholyte are separated from each other by a cation exchange membrane and in which the catholyte initially consists of water, a cosolvent, salicylic acid and a quaternary ammonium salt.

[ 51 Aug. 28, 1973 Rakoutz [54] PROCESS FOR THE PREPARATION OF 1 815,193 3/1906 Mettler 204/75 SALIGENOL 3,193,480 7/1965 Baizer 204/73 A [75] Inventor: Michel Rakoutz, Lyon, France [73] Assignee: Rhone-Poulenc S.A., Paris, France P i E mi r-F. C. Edmundson [22] Filed. Nov 18 1971 Attorney-Ellsworth H. Mosher et a1.

[2i] Appl. No.: 200,050

[57] ABSTRACT [30] F orelgn Application Priority Data 0v fame Saligenol is obtained by electrochemical reduction of 52 US. Cl. 204/75 Salicylic acid in a which and 511 Int. Cl c07b 29/06 C07C 29/00 me are Separated fmm each by a 58 Field of Search 204/75 Change membrane and which cahmyte iniialy 1 consists of water. a cosolvent, salicylic acid and a qua- 56] References Cited ternary ammonium salt.

UNITED STATES PATENTS Rl2,654 5/1907 Mettler 204/75 8 Claims, 1 Drawing Figure I I I 1 z l 1 IJITIIILIILIIIIIIAI Patenmd Aug. 28, 1973 v I 3,155,101

.1; PRQCESS FOR THE PREPARATION OF SALIGENOL a, -The-pre's'ent invention-.relates to asprocess-for the preparation of'saligenol 2-.hydroxy-benzyl alcohol) by electro-chemical reduction of salicylic acid (2- hydroxy-benz oic acid).

It is known that some juxtanuclear aromatic. acids can be'reduced to thecorresponding alcohols by electro-chemical reduction [C. METTLER Ber 38, 1745-1753 (1905) :Ber 39,.2933-2942 (1906) ;German Pat. Specification No] 177,490 and Friedlander 8,148 50']. The techniques described in these various essent-ially involved carrying out an eleca catholyte which was a mixture of ethyl utphurid'acid'and-the carboxylic acid to'be reduced'i :11 1 W lien such methods-were used for the preparation of saligenol? by eIectro che'micaI reduction of salicylic acid} MET FBERindicates (Ber 38, 1748) that the reac'tion l'aeks speed-and (Ber 39,2935) that it presents difficulties; These'facts are confirmed by F. SOMLO [Zeitshi *El'ektrochem 35 (10) 773 (1929) 1 who, iiiidef thgene'ral conditions described by METTLER, ohly olitained 'saligenol in electrical yields of less than 6.3 percent, these yields even falling to zero in certain cases (in which-case the electro-chemical reduction '3 According tothe present invention, a new process is provided for the preparation ofsaligenol by *electrochemical reduetio'n ot salicylic acid which" does not suffer from the disadvantages of the' known processes.

The process according to the invention consists of carrying out the electrolysis in ace having an anode compartment anda cathode com'partme'nt separated frfiin'oneirhdtli'er by'a cation exchange membrane, and means-lyre, itially consisting" essentially of salicylic seawater; osolvnt and a 'quartemary ammonium saltifiiiee theelectrolysis'has 'commencedgpart 'of the salicylic ci'd'will be' converted to saligenol and the willthen',ofco'ursemontain saligenol ina'ddie othercom'ponents mentioned previously. Th-n ure'of the cationfexchange membrane, which separates-"the catholyte from the anolyte is not critical tiftheinventionflt'is possible to use any known cation eitliange membi-ane and, in particular, homogeneoustype membranes or heterogeneous-type membranes Which ii desi'redQCan be reinforced by a screen. In order to be able to carry out electrolysis operations of long duration, it 'is preferred touse membranes which donot swell-and aif' stable'undrthe influence of the various constituents bf the'eatl'iolyte' and of theanolyte, espee ially the cosolvent. Membranes which can be used, inelude th s'e described'in the following patentspecificatibfl 'r -.."-"I.*;:- v 1 a US. Pat. No. 2,681,320. i "France-Pat. Nos. 1,568,994, 1,575,782, 1,578,019, 1,583,08'9E-'1', 5 84,187 and 2,040,950.

The e'atholyte can contain one or two liquid phases. If it contains twoliquid phases, it is preferred to carry out th proce'ss in such a way that the catholyte is in the forhFof an-emiilsion,for example by stirring or by circulating theliquid.

The-'bosolveiitcontained in the catholyte is a solvent fdr salieylid acid,- fwhich=is preferably chemically inert towards' salieylicacid unde'r'th'e're'action conditions, is eIEctYdchemiCaIIyfinert at potentials between O'and- '2 2.5.- volt ,re a veto t amra s salsmc ode. andhas adi l c ic ons nt ,oflss time. Cos ems whichxciantbe usedineludealcohols, ethers, nitriles, aliphatic amides and aliphatic; esters. The cosolvent preferablycontains'oneto 10 carbon atorns. Cosolvents which:can be used in a one liquid phase.;catho lyt e-,-,i;n,- elude methanol, ethanol, n-propanol, isopropanol, ace} tonitrile, l-methoxy-ethanol-Z, -.l;,;- 2- dii nethoxy-ethane, glyeol,.. ll-ethoxy -ethanol L l 2 i-.d iethoxy-ethane, tetrahydrofurane, dioxane, 1,2-ethanediol diacetate and .dimethylformamide. v I The proportion of cosolven n. the. water-eosolvent mixture present .in the catholy te depends, on the ability of the cosolvent to dissolve salicylic, acid. The proportion is usually between LO. and percentby weight, preferably between 45 and BQpercent by weight. The concentration of salicylic acid in the eatholyte is advantageously above 35 g/litre andbelow the satura; tion value in the water/cosolvent/qu'artemary ammo nium salt mixture.v in question these limiting values apply to the initial acid concentration vin discontinuous processes, and to the instantaneous acideoncentration in continuous processes. v 1 The quartemary ammonium salts used in the catholyte are essentially saltsof the generalfformula':

184 repre nt jds t s or airfe'rem y rd s'rbo 'ia1si; eac Having from 1 to 20 carbon.atorns'in hain orfin whielitwo of the R radicalistogether form a single divalent radical and together with fthejriitrogen -atorrl to which they are attached, form a heteroeycliering. a

The radicals R fR j R R; can represent linear or branched alkyl radicals, s'iich as methyl, ethyl, propyl, isopropyLbutyl, pentyl, hexyl, heptyl, octyl, 2-1ethyllhexylor dodecyl, cyeloalkyl or a'lltyl-cycloalltyl radicals such as cyclohexyl, or aryl radicals such as phenyl, tolyl or xylyL Examples of cations whichmay be derived from salts of formula (I) are tetramethylammonium, trimethyle thylammoniurn, methyltriethyl-ammonium, tetraetl'iyl ammonium," tetra(n-propyl)ammoniuiri-, tetra(nbutyl')ammonium, ftetra" ri-pe'ntyl )ammoiiium, 'triethy'lbutylammoniuni," triethylliexylarnmonium, triethyl(2- ethyl-hex'yUammonium triethyKn-octyUarnmOnium; trieth'yl(n-d odecybammoniuni, 'and' tributyKn dOdec'yDainr'nbniri'm ions. f I

\ The nature "of the anion A "of the salts of the formula (I) is not critieal' since "the anion cannot be reduced hi n h o him,

electrochemically under the reaction conditions. Pref erably, anions-are used such that the acid AH has a pit less than or equal to the p14 'of the aromatic carboxylie The anion A can be' -such" that AH is an inorganic acid'or anorgani'e acidJ-Examples of such inorganic undissoeiated acid 3 acids AH include sulphuric, phosphoric, pyrophosphoric, hydrochloric, hydrobromic, hydriodic, perchloric, boric and fluoboric acids. Examples of such organic acids AH include formic, malonic, methanesulphonic, ethanesulphonic, benzene-sulphonic, toluenesulphonic, methylsulphuric, ethylsulphuric acid, and salicylic acid.

Specific quarternary ammonium salts of formula (I) which may be used are tetramethylammonium, tetraethylammonium, tetra(n-b'utyl)ammonium, tetra(n-pentyl)ammonium, triethyl(n-hexyl)ammonium, triethyl(n-octyl)ammon'ium, triethyl(2-ethylhexyl) ammonium, and triethyl( n-dodecyl)-ammonium sulphates, phosphates and halides.

Apart from the various constituents of the catholyte which have been specified above, the catholyte can contain other products, especially products which are inert under the operating conditions and by-products of the electrochemical reduction.

The cathode'in the cell utilised in the process of the invention can be a metal, especially mercury or a solid amalgam of mercury.

An aqueous acid solution is preferably used as the anolyte. The precise nature of this anolyte is not criticalclude metals and metalloids such as lead and its alloys,

platinum, platinised titanium and graphite. .The'cu'rrent density at the cathode is generally 1 to 25 A/dm preferably 5 to A/dm'.

The temperature at which the electrolysis is carried out is generally 5' to 60 C and preferably 25' to C.

' Atthe end of the electrolysis (when operated discontinuously) or during electrolysis (if operated continuo'usly), the saligenol is isolated from the catholyte by any of the'known methods, for example by solvent extraction. According to a preferred procedure, the cosolvent, is first removed, for example by distillation,

which causes precipitation of any unreduced salicylic acid which may be present thisacid is filtered off and the filtrate is then extracted with ether or with another saligenol solvent which is immiscible with water on evaporating the latter solvent, saligenol is obtained. Where the precipitation of the salicylic acid during the removal ,of the cosolvent has only been partial, the residual'salicylic acid in solution can be converted into a dance with any known techniques, for example, in devices such as filter-press systems.

The process according to the invention can be carried out continuously or discontinuously. The process allows saligenol to be obtained in good electrical yields and chemical yields in a process where the electrodes, especially the cathode, are not chemically degraged by the electrolyte.

Saligenol is a starting material used in the synthesis of coumarine. I

EXAMPLE 1 The electrical cell used is that shown in the FIGURE of the accompanying drawing. The cell comprises a main trough 1 having an outer jacket 2 through which liquid at a controlled predetermined temperature may be circulated. Main trough l is divided up into a cathode compartmentcontainingcatholyte 4 and cathode 3 and an anode compartment containing anolyte 7 and anode 6. Catholyte 4 and anolyte-7 are separated from one another by cation exchange membrane 5 and internal cell divider 9. The cathode compartment is provided with amag'netic stirrer 8, thermometer l0 and a gas outlet 12 to remove gas evolved from the cathode compartment. Outlet 12 leads to a gas flow rate mea suring device (not shown).

The electrolysisconditions are as follows: Cathode lead amalgam discof surface area 0.6 dm' (prepared by immersing a disc of lead in a bath mercury for 10 hours) i Catholyte initially a mixture consisting of 250 cm of isopropanol 80 cm of water 45 g of salicylic acid and 30 g of tetraethylammonium bromide.

- Cathode cation exchange membrane distance 2 cm. Cation exchange membrane heterogeneous-type membrane having a matrix of. polyvinylidene fluoride the cation exchange resin is a sulphonic resin bmd on polystyrene crosslinked with divinylbenaene' the ex change capacity of the membrane is 1.05 meg/g its substitution resistance is 9.6 0 cm! men 0.1 N aqueous solution of NaCl and 4.8 0 cm in a normal aqueous solution of NaCl the permeation selectivity of the mem- I brane, measured between two aqueous NaCl solutions which are respectively normal and half-normal, is 96.2

percent.

Ari'ol'y'te'i 10%5y weight aqueous solution of sulphuric ac d. Anode: lead disc of surface area 0.125 dm' Anode/cation exchange membrane distance l cm Temperature: between 30' and 35' C which ensures that the medium is homogeneous.

Current density at the cathode: 6.66 Aldm' until 61,910 coulombs have been passed thereafter 7.5

The electrolysis is stopped after 80,000 coulombs have passed. 3350 cmof hydrogen (measured at 0 C under a pressure of 760 mm Hg) are collected from outlet (12).

The catholyte is 20 mm of mercury, which allows the isopropanolto be removed and causes a precipitate to form. The precipitate is filtered off and washed with water, and the filtrate and the wash waters are combined and neutralised (pH I 7) with sodium bicarbonate. The mixture is extracted with ether, the ether phase driedby means of.

distilled under a reduced pressure of sodium sulphate and concentrated to dryness l4.8 g of saligenol are obtained.

The yield of saligenol based on the acid converted is 66.6 percent while the electricalyield is 57.6 percent.

EXAMPLE 2 Example 1 is repeated, replacing the isopropanol by methanol and using a constant current density of 6.66 A/dm at the cathode. After passing 84,500 coulombs and treating the catholyte as described in Example 1, 11.1 g of saligenol are obtained.

This corresponds to a yield based on acid converted of 48.7 percent and an electrical yield of 41 percent.

EXAMPL 3 Example 1 is repeated with the following modifications:

Composition of the catholyte:

250 cm of water 250 cm is isopropanol 45 g of salicylic acid 40 g of tetraethylammonium bromide.

The current density at the cathode is constant and equal to A/dm, After passing 49,720 coulombs and treating the catholyte as described in Example 1, 7.2 g of saligenol are obtained. This corresponds to a yield based on acid converted of 79 percent and an electrical yield of 45 percent.

1 claim:

1. Process for the preparation of saligenol by electrochemical reduction of salicyclic acid in an electrolysis cell having a cathode compartment and an anode compartment, separated from one another by a cation exchange membrane and a catholyte initially consisting essentially of salicylic acid, water, a cosolvent and a quaternary ammonium salt of the general formula:

in which each of R R,, R and R represent identical or different hydrocarbon radicals, each having from 1 to 20 carbon atoms in their chain, or in which two of the R radicals together form a single divalent radiacal and together with the nitrogen atom to which they are attached, form a heterocyclic ring and A represents an anion.

2. Process according to claim 1, wherein the cosolvent is present in proportions by weight of 10 to percent in the water-cosolvent mixture contained in the catholyte.

3. Process according to claim 1, wherein the cosolvent is chemically inert under the reaction conditions towards the acid to be reduced, which is electrochemically inert at potentials of between 0 and 2.5 volts relative to the saturated calomel electrode, and which has a dielectric constant of less than 50 i 4. Process according to claim 3, wherein the cosolvent is selected from the group consisting of an alcohol, an ether, a nitrile and an aliphatic acid.

5. Process according to claim 1, wherein the current density at the cathode is l to 25 A/dm 6. Process according to claim 1, wherein the anolyte consists essentially of an aqueous acid solution.

7. Process according to claim I, wherein the quaternary ammonium salt is a tetra-alkylammonium sulphate, phosphate or halide in which each alkyl group contains 1-20 carbon atoms.

8. Process according to claim 1, wherein the anolyte is aqueous sulphuric acid, the catholyte initially consists essentially tetra-alkyl-ammonium salicylic acid, water, methanol or isopropanol and a tetra-alkalyammonium bromide and electrolysis is carried out at a current density at the cathode of 5-l5 A/dm. 

2. Process according to claim 1, wherein the cosolvent is present in Proportions by weight of 10 to 90 percent in the water-cosolvent mixture contained in the catholyte.
 3. Process according to claim 1, wherein the cosolvent is chemically inert under the reaction conditions towards the acid to be reduced, which is electrochemically inert at potentials of between 0 and -2.5 volts relative to the saturated calomel electrode, and which has a dielectric constant of less than
 50. 4. Process according to claim 3, wherein the cosolvent is selected from the group consisting of an alcohol, an ether, a nitrile and an aliphatic acid.
 5. Process according to claim 1, wherein the current density at the cathode is 1 to 25 A/dm2.
 6. Process according to claim 1, wherein the anolyte consists essentially of an aqueous acid solution.
 7. Process according to claim 1, wherein the quaternary ammonium salt is a tetra-alkylammonium sulphate, phosphate or halide in which each alkyl group contains 1-20 carbon atoms
 8. Process according to claim 1, wherein the anolyte is aqueous sulphuric acid, the catholyte initially consists essentially tetra-alkyl-ammonium salicylic acid, water, methanol or isopropanol and a tetra-alkaly-ammonium bromide and electrolysis is carried out at a current density at the cathode of 5-15 A/dm2. 